Angiogenic activity of sera from interstitial lung disease patients in relation to clinical and radiological changes

Zielonka Tm, Demkow U, Zycinska K, Filewska M, Bialas B, Kus J, Radzikowska E, Remiszewski P, Szopinski J, Soszka A, Wardyn Ka, Skopinska-Rozewska E

Description

Objective Clinical symptoms and radiological changes are useful in monitoring patients with interstitial lung diseases (ILD). Neovascularization participates in the pathogenesis of idiopathic pulmonary fibrosis and other ILD. The objective of the study was to examine the relationships between angiogenic activity of sera from ILD patients and clinical or radiological status. Material and methods Serum samples were obtained from 83 patients with sarcoidosis, 31 with idiopathic pulmonary fibrosis (IPF), 29 with hypersensitivity pneumonitis (HP), 16 with collagen diseases with pulmonary manifestation (CD), 13 with scleroderma (SCL), 14 with Wegener's granulomatosis (WG), 12 with pulmonary Langerhans cell histiocytosis (HIS), 12 with pneumoconiosis (PNC), 10 with drug-induced lung disease (DLD), 5 with cryptogenic organizing pneumonia (COP), and from 36 healthy volunteers. As an angiogenic test we used a cutaneous angiogenesis assay according to Sidky and Auerbach. Clinical status was evaluated using a special questionnaire. In all patients chest radiographs were performed. Results The angiogenic properties of sera from ILD differed depending on the clinical diagnosis. The strongest proangiogenic effect was induced by sera from patients with HP (mean number of new vessels 16.8), CD (16.6), sarcoidosis (16.3), IPF (16.2), and PNC (15.7). In the case of DLD (13.2), the effect was comparable to healthy controls (13.5). In contrast, sera from SCL (mean number of the vessels 10.5) and HIS patients (10.8) significantly inhibited angiogenesis compared with controls. The angiogenic activity of sera from patients with hilar or mediastinal lymph nodes involvement was higher than that of sera from patients with lung fibrosis. There were also differences in the serum angiogenic activity in relation to the severity of dyspnea. Conclusions The data showed that sera from ILD patients constitute a source of mediators modulating angiogenesis, but the pattern of reaction is different in various diseases. Sera from HP, sarcoidosis, IPF, and CD patients demonstrated the strongest proangiogenic activity. However, sera from SCL and HIS inhibit angiogenesis. Angiogenic activity of examined sera was related to the clinical and radiological changes.

Sujets

• Angiogénesis

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 4
• Langue: English

Extrait

December 7, 2009

EUROPEAN JOURNAL OF MEDICAL RESEARCH

Eur J Med Res (2009) 14(Suppl. IV): 259-264

259

© I. Holzapfel Publishers 2009

A NGIOGENIC A CTIVITY OF S ERA FROM I NTERSTITIAL L UNG D ISEASE P ATIENTS IN R ELATION TO C LINICAL AND R ADIOLOGICAL C HANGES

1 2 1 33 33 T. M. Zielonka , U. Demkow , K. Zycinska , M. Filewska , B. Bialas , J. Kus , E. Radzikowska , 3 33 14 P. Remiszewski , J. Szopinski , A. Soszka , K. A. Wardyn , E. Skopinska-Rozewska

1 2 Department ofFamily Medicine andDepartment ofLaboratory Diagnostics and Clinical Immunology ofDevelopmental Age, Warsaw 3 Medical University, Warsaw, Poland;Institute ofTuberculosis and Lung Diseases, Warsaw, Poland; 4 Department ofPathology, Biostructure Center, Warsaw Medical University, Warsaw, Poland

Abstract Objective:Clinical symptoms and radiological changes are useful in monitoring patients with interstitial lung diseases (ILD). Neovascularization participates in the pathogenesis ofidiopathic pulmonary fibrosis and other ILD. The objective ofthe study was to examine the relationships between angiogenic activity ofsera from ILD patients and clinical or radiological status. Material and methods:Serum samples were obtained from 83 patients with sarcoidosis, 31 with idiopathic pulmonary fibrosis (IPF), 29 with hypersensitivity pneumonitis (HP), 16 with collagen diseases with pul- monary manifestation (CD), 13 with scleroderma (SCL), 14 with Wegener’s granulomatosis (WG), 12 with pulmonary Langerhans cell histiocytosis (HIS), 12 with pneumoconiosis (PNC), 10 with drug-induced lung disease (DLD), 5 with cryptogenic organizing pneumonia (COP), and from 36 healthy volunteers. As an angiogenic test we used a cutaneous angiogenesis assay according to Sidky and Auerbach. Clinical status was evaluated using a special questionnaire. In all pa- tients chest radiographs were performed. Results:The angiogenic properties ofsera from ILD differed depending on the clinical diagnosis. The strongest proangiogenic effect was induced by sera from patients with HP (mean number ofnew vessels 16.8), CD (16.6), sarcoidosis (16.3), IPF (16.2), and PNC (15.7). In the case ofDLD (13.2), the effect was comparable to healthy controls (13.5). In contrast, sera from SCL (mean number ofthe vessels 10.5) and HIS patients (10.8) significantly inhibited angiogenesis compared with controls. The angiogenic activity of sera from patients with hilar or mediastinal lymph nodes involvement was higher than that ofsera from patients with lung fibrosis. There were also differences in the serum angiogenic activity in relation to the severity ofdyspnea. Conclusions:The data showed that sera from ILD pa- tients constitute a source ofmediators modulating an- giogenesis, but the pattern ofreaction is different in various diseases. Sera from HP, sarcoidosis, IPF, and CD patients demonstrated the strongest proangio- genic activity. However, sera from SCL and HIS inhib- it angiogenesis. Angiogenic activity ofexamined sera was related to the clinical and radiological changes.

Key words:angiogenesis, interstitial lung diseases, clini- cal symptoms, radiological changes

I NTRODUCTION

Angiogenesis, a process ofnew capillary formation from pre-existing vessels, is an important biological event occurring in many physiological and pathologi- cal processes, such as an embryonic development, for- mation ofan inflammatory granulation during wound healing, chronic inflammation, and the growth ofma- lignant solid tumors [1-4]. Vessel formation is a multi- step process which requires endothelial cell migration, proliferation and degradation ofextracellular matrix, and capillary tube formation which is mediated by var- ious angiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin 8 (IL-8), and others [5]. In con- trast, the precise regulation ofangiogenesis during wound healing, tumor angiogenesis is characterized by an imbalance between pro-angiogenic and antiangio- genic growth factors and cytokines [6]. Chronic fibro- proliferative disorders such as pulmonary fibrosis are also associated with aberrant angiogenesis [7]. Idio- pathic pulmonary fibrosis and fibrosing alveolitis asso- ciated with systemic sclerosis are characterized by a substantial vascular redistribution, with a shift ofin- terstitial vessels away from airspaces [7]. Vascular re- modeling was observed in the fibrotic areas ofthe lungs but the relevance ofthese findings in relation to the pathophysiology offibrosing alveolitis requires further investigation. Other interstitial lung diseases (ILD) characterized by inflammation, cell prolifera- tion, excessive extracellular matrix deposition and sev- eral cytokines, are also characterized by aberrant an- giogenesis, playing an important role in their patho- genesis [8]. CXC chemokines such as IL-8 and epithe- lial neutrophil activating protein 78 are involved in the control ofthe angiogenesis [9]. Previously, we demon- strated that serum angiogenic activity in a number of ILD, such as sarcoidosis, pulmonary fibrosis, and sili- cosis, is enhanced [10-12]. Although our knowledge on mechanisms ofneo- vascularization on the cellular level has been constant- ly increasing, little is known to what extend neovascu-